Progress in synthesizing protocells

Abstract

Advances in the understanding of the biophysics of membranes, the nonenzymatic and enzymatic polymerization of RNA, and in the design of complex chemical reaction networks have led to a new, integrated way of viewing the shared chemistry needed to sustain life. Although a protocell capable of Darwinian evolution has yet to be built, the seemingly disparate pieces are beginning to fit together. At the very least, better cellular mimics are on the horizon that will likely teach us much about the physicochemical underpinnings of cellular life.

Keywords: Protocell; RNA world; minimal cell; origin of life; peptides; prebiotic chemistry; protometabolism; vesicles.

Figure 1.

Schematic of one conception of a hypothetical protocell. A chemical reaction network within a lipid vesicle acquires nutrients that lead to the copying of nucleic acids and the synthesis of peptides and lipids. Here, the internal chemistry of the protocell supports membrane growth by synthesizing lipid. Membrane growth then leads to the division of unstable intermediate structures through environmental shear forces. Reactive monomeric building blocks and reaction by-products, i.e. waste, passively diffuse across the membrane. Ideally, an internal protometabolic network would sustain the protocell across many generations.

Figure 2.

The lipids and lipid dynamics of protocellular membranes. (a) From top to bottom, the structures of model prebiotic lipids are decanoic acid, decanol, the glycerol monoester of decanoate, and cyclic-lyso-phosphodecanoic acid. The last structure is of di-decanoyl phosphatidic acid, shown for reference. (b) Above the critical aggregate concentration, fatty acids exist in equilibrium between free monomers, micelles (green), and various lipid aggregates (purple), including vesicles with bilayer membranes. Lipid monomers can be exchanged between different aggregate structures, flip between leaflets (blue), and laterally diffuse (yellow). The dynamic nature of the bilayer may lead to the formation of transient pores. Micelles can incorporate into pre-existing vesicles, leading to a net growth in volume and surface and surface area (green). Likewise, the presence of diacyl phospholipids (brown) leads to vesicle growth through the net accumulation of fatty acid (orange) by decreasing the desorption rate of fatty acids from the membrane.

Figure 3.

Transition towards a functional protocell. A subset of complex prebiotic chemistry gave rise to protocells. Here, the process is envisaged to have proceeded in a fashion where nucleic acids were deeply integrated with peptides, and metabolic-like chemistry to generate a cell-like network from the beginning. That is, systems did not generally evolve separately and later merge. Iterative cycles of growth, fusion, and division ultimately led to competition between protocells sustained by some type of dissipative chemical (proto)metabolism.